Mette Olufsen

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  Cardiovascular control in patients with orthostatic intolerance
  Mette Olufsen

  The state of the cardiovascular system can be assessed from time-series signals including heart rate and blood pressure. Characteristics of these signals are used to determine pathophysiology. Experienced clinicians can visually inspect signals and with high level of certainty determine key observed dynamics however analysis with computational models can uncover the underlying mechanisms driving these dynamics. This talk will address how mathematical modeling can be adapted to match patient specific behavior and how the optimized system equations can be used to predict emergent behavior. Sensitivity analysis, parameter estimation, and uncertainty quantification are mathematical tools used analyze models for individual patients. Focus will be on studying dynamics observed in patients diagnosed with postural orthostatic tachycardia (increased heart rate brought on by change in posture, e.g. sit to stand) observed in some girls after vaccination against the human papilloma virus (HPV). Girls exhibiting side-effects to this vaccine often feel dizzy, light-headed, and tired. It is believed that these symptoms are related to pathophysiology within the cardiovascular control system, which is supposed to keep heart rate and blood pressure constant. To understand how the system is impacted we use models to analyze patient specific changes observed during head-up tilt, Valsalva (breath holding), and deep breathing.

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  Modeling blood pressure and heart rate dynamics in patients with orthostatic intolerance
  Mette Olufsen

  Orthostatic intolerance occurs when a transition to standing upright causes an imbalance in blood pressure and flow. It affects an estimated 500,000 Americans in particular young women (the female-to-male ratio is approximately 5:1). Symptoms of this disorder range from lightheadedness to fainting. Because many diseases exhibit these symptoms, this disorder can be difficult to diagnose. Moreover, several competing hypotheses have been put forward to explain this disorder, including imbalance of the blood volume regulation and reduced efficacy of the baroreflex control system. The most common tests performed to assess a patient's health are the head-up-tilt and sit-to-stand tests. These tests are designed to stimulate the cardiovascular control system via a simple change of body posture from supine to sitting or standing position. In response to the postural change, blood volume is pooled in the legs leading to a drop in blood pressure in the upper body. The blood pressure drop stimulates baroreceptor neurons, which, via sympathetic stimulation and parasympathetic withdrawal, regulate the heart pumping function and vessel properties facilitating return of blood flow and pressure to their homeostatic levels. This regulation is often disrupted in patients with orthostatic intolerance, often experienced by patients with diabetes, hypertension, and other neurological diseases of which Parkinson’s disease is the most prevalent. The autonomic nervous system is composed of many interacting components, yet measurements done to assess the system are typically limited to heart rate and blood pressure. One way to gain more understanding of the system is via mathematical modeling. This talk will demonstrate what insights can be learned using multiscale models predicting cardiovascular dynamics and the associated autonomic control.